Viral-Bacterial Co-infections in the Cystic Fibrosis Respiratory Tract

Abstract

A majority of the morbidity and mortality associated with the genetic disease Cystic Fibrosis (CF) is due to lung disease resulting from chronic respiratory infections. The CF airways become chronically colonized with bacteria in childhood, and over time commensal lung microbes are displaced by bacterial pathogens, leading to a decrease in microbial diversity that correlates with declining patient health. Infection with the pathogen Pseudomonas aeruginosa is a major predictor of morbidity and mortality in CF, with CF individuals often becoming chronically colonized with P. aeruginosa in early adulthood and thereafter having an increased risk of hospitalization. Progression of CF respiratory disease is also influenced by infection with respiratory viruses. Children and adults with CF experience frequent respiratory viral infections with respiratory syncytial virus (RSV), rhinovirus, influenza, parainfluenza, and adenovirus, with RSV and influenza infection linked to the greatest decreases in lung function. Along with directly causing severe respiratory symptoms in CF populations, the impact of respiratory virus infections may be more far-reaching, indirectly promoting bacterial persistence and pathogenesis in the CF respiratory tract. Acquisition of P. aeruginosa in CF patients correlates with seasonal respiratory virus infections, and CF patients colonized with P. aeruginosa experience increased severe exacerbations and declines in lung function during respiratory viral co-infection. In light of such observations, efforts to better understand the impact of viral-bacterial co-infections in the CF airways have been a focus of clinical and basic research in recent years. This review summarizes what has been learned about the interactions between viruses and bacteria in the CF upper and lower respiratory tract and how co-infections impact the health of individuals with CF.

Keywords: biofilm; chronic disease; coinfection; cystic fibrosis; polymicrobial; respiratory infection.

Figure 1

Summary of respiratory virus infection outcomes impacting viral-bacterial interactions in Cystic Fibrosis. Acute respiratory viral infections are known to affect subsequent infection with bacterial pathogens and influence pre-existing chronic bacterial infections in individuals with Cystic Fibrosis. Some ways in which respiratory viruses have been shown to impact bacterial infections include: inducing the host immune response; altering metabolic output of both host and infecting bacteria; causing new bacterial acquisition in patients who were previously culture-negative; altering bacterial community composition by shifting relative abundance of specific bacterial species; and inducing fluctuations in total bacterial burden.